An estimated 20 million people in the US are exposed to levels of arsenic in their drinking water near or above the current regulatory standard. The developing lung may be particularly susceptible to environmental toxicants including arsenic. Previous studies from northern Chile suggest that people exposed to arsenic in water as young children or in utero have relative risks of lung cancer that are 3-4 times higher than those exposed as adults. Several studies have also linked arsenic in water to very high risks of non-malignant lung disease, but these have not assessed the possible long-lasting or permanent effects of exposure during the critical periods of lung development. We propose a cross-sectional study of pulmonary function (measured by spirometry) and respiratory health in subjects from northern Chile who were exposed to high arsenic levels as young children or in utero and who are now adults. We will recruit 300 lifelong residents of the city of Antofagasta which had very high arsenic concentrations in municipal water supplies from 1958 to 1970. Measures of pulmonary function and prevalence of respiratory symptoms in these subjects will be compared to 300 age- and gender-matched lifelong residents of Arica, a neighboring sociodemographically similar city with no history of high arsenic levels. All subjects will be randomly selected from the Chile Electoral Registry which contains 94% of the Chilean population. Urine samples will be collected for future biomarker studies of susceptibility and early effects. The advantage of doing this study in northern Chile is that this area is incredibly dry and almost everyone lives in one the few large cities and obtains water from one of a few large municipal water supplies. Because we have arsenic records for all these sources for the last 50 years, information on lifetime exposure can be much more accurate than anywhere else in the world. Also, a distinct period of high exposure occurring in Antofagasta about 40 years ago, with low exposure before and after, has created a large population (about 250,000) who were highly exposed in utero or as young children but not as adults. Studying health effects in these people now will allow us to investigate the long-term impacts of their early life exposure. A scenario like this, with its distinct period of high exposure, large population, high exposure in early life but not in adulthood, and accurate data on past exposure, is without precedent in environmental epidemiology. The scientific importance of this project lies in the fact that little information is available in humans on the lifelong effects of environmental exposures that occur during critical periods of lung development. The public health importance lies in the need to incorporate information on early life exposure effects into environmental regulation, and in helping to assess whether more rigorous public health measures are needed to identify and prevent toxic exposures in children and pregnant women. PUBLIC HEALTH RELEVANCE: Arsenic exposure from drinking water is a widespread health hazard throughout the world. This study will help reveal important new information concerning the long term health impact of childhood exposure to arsenic. It will also help determine whether other factors such as diet or tobacco smoke exposure can interact with arsenic to cause long term lung disease.